[Cardiovascular diseases burden attributed to low physical activity in China, 1990-2019].

Objective: To analyze the burden of cardiovascular disease (CVD) attributed to low physical activity (LPA) and its changing trends in China from 1990 to 2019. Methods: On the basis of the province results of the Study of Global Burden of Disease 2019 in China, we described the distribution of CVD death and disability-adjusted life year (DALY) attributed to LPA by sex, age and province. Joinpoint 4.9.1.0 was used to calculate the average annual percentage change. Results: In 2019, the number of CVD deaths and DALY attributed to LPA in people aged ≥25 years were 0.127 million and 1.863 million person-years in China, respectively, The age-standardized mortality rate (ASMR) and standardized DALY rate of CVD attributed to LPA were slightly higher in men than in women, and much higher in ischemic heart disease patients than in ischemic stroke patients. The ASMR (8.85/100 000) and the standardized DALY rate (112.34/100 000) of CVD attributed to LPA in China in 2019 showed no obvious change compared with 1990, while decreased in the last decade. The largest increases in the mortality rate and DALY rate were observed in people aged ≥75 years from 1990 to 2019 (26.89%, 15.61%), but the mortality rate and DALY rate in people aged 60-74 years showed a decreasing trend. The mortality rate and DALY rate in men aged 25- 44 years showed the largest increases (37.50%, 35.49%), while women aged ≥75 years had the largest increases (31.00%, 18.02%). In 2019, the highest ASMR and standardized DALY rate of CVD attributed to LPA were found in Jilin, Inner Mongolia and Hebei. The largest increases were found in Qinghai (182.41%, 154.70%), Gansu (181.29%, 152.77%), and Chongqing (132.01%, 102.79%) and the largest decreases were found in Beijing (59.11%, 62.09%), Macau (41.89%, 39.37%) and Guangdong (36.93%, 40.72%) from 1990 to 2019. Conclusion: The disease burden of CVD attributed to LPA in China was quite high and showed gender, age and area specific differences.

Partial cellular reprogramming stably restores the stemness of senescent epidermal stem cells.

OBJECTIVE: Adult stem cell senescence and exhaustion are important drivers of organismal age. Restored stem cell self-renewal has revealed novel therapeutic targets for decreasing the incidence of age-associated diseases (AADs) and prolonging the human health span. Transient ectopic expression of the reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc (collectively known as OSKM) in somatic cells can induce partial cellular reprogramming and effectively ameliorate their age-associated hallmarks. However, how this form of rejuvenation is applied to senescent stem cells remains unknown. MATERIALS AND METHODS: The Integrin-α6highCD71high epidermal stem cells (ESCs) with low self-renewal ability were sorted by flow cytometry and then treated by the interrupted reprogramming induced by transient expression of OSKM. The ability of secondary clones' generation and self-proliferation in vitro, as well as stem cell marker p63, were detected to determine their self-renewal ability. Besides, gene and protein of epidermal cell markers were detected to determine whether their cell identities were retained. Finally, DNA methylation age (eAge) and DNA dehydroxymethylase/methyltransferase were analyzed to explore the alternation of their global DNA methylation pattern during this rejuvenation. RESULTS: The partial reprogramming restored the youthful self-renewal and proliferation in senescent ESCs, including larger secondary clone generation, higher expression of stem cell marker p63 and proliferation marker Ki67, and faster proliferation speed, in each case without abolishing epithelial cellular identity. Moreover, the rejuvenation of adult stem cells could be maintained for 2 weeks after reprogramming factor withdrawal, which was more stable than that of differentiated somatic cells. Additionally, we found that partial reprogramming counteracted the acceleration of eAge in senescent epidermal stem cells and DNA methyltransferase 1 (DNMT1) may play a crucial role in this process. CONCLUSIONS: Partial reprogramming has high therapeutic potential for reversing adult stem cell age, providing an advanced way to treat AADs.

[Clinical observation of superior rectus transposition with/without augmented suture and vertical rectus transposition for the treatment of strabismus caused by complete abducens nerve palsy].

Objective: To evaluate the efficacy and safety of superior rectus transposition (SRT) with/without augmented suture and vertical rectus transposition (VRT) for the treatment of strabismus caused by complete abducens nerve palsy. Methods: This was a retrospective cohort study. Forty-two patients (42 eyes) with complete abducens nerve palsy underwent strabismic surgeries from January 2015 to November 2020 in Tianjin Eye Hospital. According to the different procedures, the patients were divided into three groups: SRT group (16 cases, SRT with medial rectus recession), superior rectus transposition with augmented suture (SRTA) group (13 cases, SRT with Buckley suture and medial rectus recession) and VRT group (13 cases). The preoperative and postoperative (1, 6 and 12 months) data including deviations, ocular motility, binocular vision and surgical complications among three groups were analyzed and compared. χ2 test was used for comparison of count data among three groups. The measurement data were compared among three groups by the repeated measures ANOVA. LSD-t test was used for within-group comparison and between-group comparison. Results: There was no difference in sex ratio, age and course of disease among the groups (all P>0.05). The horizontal deviations of the three groups at 1, 6 and 12 months after surgeries was lower than that before surgeries, and the difference was statistically significant (all P<0.001). The horizontal deviations of the SRT group, SRTA group and VRT group at 12 months after surgeries were (+0.8±5.8), (+0.8±4.5), (+1.2±2.5) prism diopters (PD), respectively, lower than that of the preoperative (+82.8±17.2), (+77.7±26.1), (+71.5±18.6) PD. However, there was no significant difference among different postoperative follow-up timepoints (all P>0.05). There was no difference in horizontal deviations before surgeries and at 1, 6 and 12 months after surgeries among three groups (P>0.05). There were significant differences in the scales of abduction motility among preoperative, postoperative 1, 6 and 12 months measurements for three group (all P<0.001). The scales of abduction before surgeries in the SRT group, SRTA group, and VRT group were (-4.4±0.5), (-4.4±0.5), (-4.5±0.5) scale and at 12 months after surgeries were (-2.3±0.7), (-2.2±0.5), (-2.1±0.6) scale respectively. But there was no change among different postoperative follow-up timepoints (all P>0.05). Preoperative and postoperative 1-, 6-and 12-month abduction motility was similar among three groups (P>0.05). There were significant differences in the scales of adduction limitation among preoperative, postoperative 1-, 6-and 12-months measurements for three group (all P<0.05). But there was no change among different postoperative follow-up timepoints (all P>0.05). There were significant differences between the SRT group [(-0.9±0.6), (-0.8±0.6) scale] and the SRTA groups [(-1.5±0.5), (-1.4±0.5) scale] (t=-2.62, -2.52) and between the SRTA group and the VRT group [(-0.8±0.8), (-0.6±0.7) scale] (t=2.62, 3.01) at 6 and 12 months after surgeries (all P<0.05). The outcomes of binocular vision at postoperative 12 months were similar among three groups (P>0.05). No patient had torsional diplopia and anterior segment ischemia. Only 2 patients from the SRTA group had hypotropia of 4 to 5 PD in the primary position associated with supraduction limitation. Conclusions: SRT with/without augmented suture and VRT are effective and safe procedures for the treatment of strabismus caused by complete abducens nerve palsy. They could correct deviations, improve abduction motility and restore binocular vision, with stable outcomes and a small risk of vertical and torsional diplopia.

[A real-world study of the efficacy and safety of sofosbuvir and velpatasvir in the treatment of HCV-infected patients in a county in northern China].

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.

[HIV infection status and related factors in men who have sex with men in sentinel surveillance in Shanxi province, 2010, 2015 and 2020].

Objective: To understand the infection status of HIV and related factors in men who have sex with men (MSM) in Shanxi province in 2010, 2015 and 2020. Methods: According to the sentinel surveillance protocol, continuous cross-sectional survey were conducted to collect the information about basic characteristics, general demographic characteristics, AIDS knowledge awareness, high-risk sexual behavior, sexually transmitted diseases, intervention services and HIV infection rate of the MSM in Shanxi in 2010, 2015 and 2020. Results: In 2010, 2015 and 2020, a total of 2 708 MSM were included in this study. There were significant differences in HIV infection rate among three years (χ2=23.76, P<0.001) with an increasing trend with year (trend χ2 =17.34, P<0.001). The rates of anal sex, commercial sex and heterosexual behavior in the past 6 months were 77.62% (2 102/2 708), 5.91% (160/2 708) and 28.14% (762/2 708) respectively, and the rates of consistent use of condom were 52.52% (1 104/2 102), 63.13% (101/160) and 23.49%(179/762) respectively, and the rate of consistent condom use was low. Results from multivariate logistic regression analysis showed that different cities, having educational level of junior high school or below, being recruited through internet, voluntary counseling and testing, suffering from sexually transmitted diseases, occasional condom use in anal sex in the past 6 months were the correlative factors of HIV infection of MSM. Conclusions: The HIV infection rate of MSM in Shanxi increased year by year from 2010, 2015 to 2020. The HIV/AIDS-related risk behavior persisted, and the proportion of condomuse adherence was low, and the HIV detection rate was low in the MSM, so targeted and effective measures should be taken to promote the condom use adherence and regular HIV testing in MSM.

[A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia].

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .

Effects of oregano essential oil as an antibiotic growth promoter alternative on growth performance, antioxidant status, and intestinal health of broilers.

This experiment was conducted to assess the comparative effects of dietary antibiotics and oregano essential oil (OEO) addition on growth performance, antioxidant status and intestinal health of broilers. A total of 384 one-day-old broilers were randomly allocated to 4 treatments with 6 replicates of 16 broilers each. The 4 treatments were: an antibiotic-free control diet (control), control + 20 mg/kg colistin sulfate and 20 mg/kg virginiamycin (antibiotics), control + 200 mg/kg natural oregano essential oil (NOEO), and control + 200 mg/kg synthetic oregano essential oil (SOEO). The experiment lasted for 42 d. Results showed that birds fed with OEO had greater (P < 0.05) average daily gain (ADG) and lower (P < 0.05) feed conversion ratio (FCR) than those fed with control diet during d 1 to 21. Besides, birds fed with NOEO had the greatest (P < 0.05) ADG in the four groups during d 22 to 42. The serum oxidative stress parameters showed that OEO improved (P < 0.05) the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glutathione reductase (GR) of birds on day 21 and the activity of total antioxidant capacity (T-AOC) of birds on d 42. Relative to control, NOEO increased (P < 0.05) the activity of T-AOC in jejunum and decreased (P < 0.05) the level of malondialdehyde (MDA) in serum and jejunum. Moreover, OEO supplementation increased (P < 0.05) the concentrations of sIgA in duodenum and jejunum, Lactobacillus and total anaerobes in cecum, as well as activities of trypsin, chymotrypsin, lipase and amylase in duodenum, but restrained (P < 0.05) the amount of Escherichia coli. The NOEO supplementation increased (P < 0.05) total anaerobes of broilers on d 42 and the villus height to crypt depth ratio (VH/CD) of ileum. These results suggest that OEO improved antioxidant status and intestinal health of broilers which contributed to the growth performance improvement of broilers. Dietary OEO supplementation can be a promising alternative to antibiotic growth promoters for improving poultry production.

[Comparison of prognostic significance between multiparameter flow cytometry and real-time quantitative polymerase chain reaction in the detection of minimal residual disease of Philadelphia chromosome-positive acute B lymphocytic leukemia before allogeneic hematopoietic stem cell transplantation].

Objective: To explore the different values of minimal residual disease (MRD) detection by multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (RQ-PCR) before hematopoietic stem cell transplantation (HSCT) for predicting relapse, leukemia-free survival (LFS) , and overall survival (OS) in Philadelphia chromosome-positive ALL (Ph(+) ALL) . Methods: A retrospective study (n=280) was performed. MRD was determined using multiparameter flow cytometry and RQ-PCR. Results: MRD analysis with MFC and RQ-PCR of the BCR-ABL fusion transcript showed a strong correlation before transplantation. The positive rates of MRD detected by MFC and RQ-PCR before transplantation were 25.7% (72/280) and 60.7% (170/280) , respectively. MFC MRD-positive (MRDpos) Ph(+) ALL patients had a higher 3 year cumulative incidences of relapse (CIR) than did MFC MRD-negative (MRDneg) Ph(+) ALL patients (23.6%vs 8.6%; P<0.001) . However, the RQ-PCR MRDpos group had similar rates of 3 year OS, LFS, and NRM compared with those in the RQ-PCR MRDneg group. Moreover, patients with RQ-PCR MRD ≥1% experienced higher 3 year CIR (23.1%vs 11.4%; P=0.032) , lower LFS (53.8%vs 74.4%; P=0.015) , and OS (57.7% vs 79.1%; P=0.009) compared with the RQ-PCR MRD<1% group. Multivariate analyses confirmed the association of MFC MRD status and RQ-PCR MRD ≥1% with outcomes (P<0.05) . The sensitivity, specificity, positive predictive value (PPV) , and negative predictive value (NPV) of MFC detection MRD to predict recurrence were 48.50%, 77.56%, 23.62%, and 87.16%, respectively. Moreover, the sensitivity, specificity, PPV, and NPV were 23.00%, 88.59%, 17.15%, and 91.84%, respectively, when RQ-PCR MRD ≥1% was used to predict recurrence. Additionally, the sensitivity, specificity, PPV, and NPV were 54.29%, 73.88%, 45.7% and 91.87%, respectively, when MRD-positive status before transplantation (MFC MRDpos or RQ-PCR MRD ≥1%) was used to predict recurrence after transplantation. Conclusions: Both MFC and RQ-PCR detection of pretransplant MRD levels can predict the prognosis of Ph(+) B-ALL patients receiving allogeneic HSCT. MFC MRD-positive status before transplantation is the risk factor of leukemia recurrence after transplantation. The combined use of the two methods (MFC MRDpos or RQ-PCR MRD ≥1%) can improve the sensitivity, PPV, and NPV of predicting recurrence and help to better screen high-risk patients for intervention, thereby improving clinical efficacy.

Development of an integrated multivariate trend-frequency analysis method: Spatial-temporal characteristics of climate extremes under global warming for Central Asia.

Temperature and precipitation are the two most critical climate variables and their extreme states have more severe impacts than average states on both human society and natural ecosystem. In this study, an integrated multivariate trend-frequency analysis (IMTFA) approach is developed for the risk assessment of climate extremes under the global warming. Through incorporating multiple time series analysis techniques (i.e., M-K test, Sen's slope estimator and Pettitt test) and copula function into a general framework, IMTFA is capable not only of analyzing the temporal trends and change points of extreme temperatures and precipitations, but also of quantifying their univariate and multivariate risks. IMTFA is applied to the Central Asia with considering a long-term (1881-2018) observation data. Our findings are: (i) significant wetting and warming trends were occurred in the Central Asia over past one hundred years, where 42.5%, 59.4% and 79.2% stations have change points for extreme precipitations, maximum and minimum temperatures, respectively; (ii) the occurrences of extreme climate events show obviously spatial heterogeneity, where the highest risks of meteorological drought, flood and frost events are occurred in the southwest, southeast and northeast regions, respectively; (iii) global warming significantly affects the intensities and frequencies of extreme precipitations and temperatures, and their univariate and multivariate risks are intensified in the most regions of Central Asia. The above findings can provide more valuable information for risk assessment and disaster adaptation of climate extremes in Central Asia.

Assessment of the effects of human activity and natural condition on the outflow of Syr Darya River: A stepwise-cluster factorial analysis method.

Water scarcity causes a series of eco-environmental problems, such as land salinization, biodiversity reduction and food crisis, which seriously restricts the sustainable development of the Aral Sea basin. In this study, a stepwise-cluster factorial analysis (SCFA) approach is proposed for assessing the effects of natural condition and human activity on the outflow of Syr Darya River (abbreviated as OSR) that has significant effects on the eco-environmental restoration of the Aral Sea. SCFA coupled stepwise cluster analysis and factorial analysis cannot only reflect the variability of outflow, but also identify the driving factors quantitatively. The results disclose that, in 1960-1991, the dominant factors (affecting the OSR) are upstream inflow (25.77%) > agricultural water use of Uzbekistan (7.21%) > industrial water use of Uzbekistan (4.53%) > agricultural water use of Kazakhstan (3.81%) > Precipitation (3.66%); interactions between upstream inflow and agricultural water use of Uzbekistan, Kazakhstan and Tajikistan and interactions between reservoir and evapotranspiration have the significant effects on the OSR. Results also indicate that, in 1992-2015, the dominant factors that affect the OSR are agricultural water use of Uzbekistan (23.31%) > agricultural water use of Kazakhstan (22.15%) > industrial water use of Uzbekistan (8.31%) > domestic water use of Kazakhstan (4.68%) > agricultural water use of Tajikistan (4.54%) > domestic water use of Uzbekistan (4.41%); the interactions between industrial water use and agricultural water use of Uzbekistan, Kazakhstan and Tajikistan and the interactions between reservoir and upstream inflow have the pivotal effects on OSR. In the future, when the agricultural water use of the basin decrease as 4% and the industry water use of Uzbekistan decrease as 2%, the OSR may recover to the middle level of 1970s. The results help identify the major factors affecting the outflow of Syr Darya River as well as seek an effective approach to restore the eco-environment of Aral Sea basin.

NAA10 promotes proliferation of renal cell carcinoma by upregulating UPK1B.

OBJECTIVE: The purpose of this study was to illustrate the role of NAA10 in aggravating the malignant progression of renal cell carcinoma (RCC) by upregulating UPK1B. PATIENTS AND METHODS: NAA10 levels in RCC tissues and paracancerous tissues were detected. Thereafter, the potential relationship between NAA10 level and clinical parameters of RCC patients was analyzed. After knockdown of NAA10, changes in proliferative potential of 786-O and Caki-1 cells were examined by cell counting kit-8 (CCK-8), colony formation and 5-Ethynyl-2'-deoxyuridine (EdU) assay. Finally, the regulatory role of NAA10 in the downstream gene UPK1B and the involvement of UPK1B in the development of RCC were determined via rescue experiments. RESULTS: NAA10 was upregulated in RCC tissues than paracancerous tissues. Tumor staging was much worse in RCC patients expressing a higher level of NAA10. Knockdown of NAA10 inhibited proliferative potential and downregulated UPK1B in RCC cells. Besides, NAA10 level was identified to be positively linked to UPK1B level in RCC tissues. At last, overexpression of UPK1B was able to abolish the inhibitory effect of silenced NAA10 on RCC proliferation. CONCLUSIONS: NAA10 level is closely linked to tumor staging and poor prognosis in RCC patients. NAA10 aggravates the malignant progression of RCC by upregulating UPK1B and may be a specific biomarker in RCC.

[The role of time-series propagation map and activity path of confirmed cases in the analysis and determination of COVID-19 epidemic].

Objective: The time sequence transmission map and the cases travel track were used to explain the chain of transmission, describe the characteristics of transmission and analyze the mode of epidemic of novel coronavirus pneumonia, so as to provide evidence for the relevant government departments to carry out epidemic prevention and control. Methods: The time sequence transmission map and the cases travel track table were drawn, according to the time of incidence, age, sex, number of close contacts and their interrelations. Results: At the end of February 10, 2020, 63 COVID-19 cases were reported in the research area. Among them, 57 cases were confirmed (1 deaths) and 6 cases were asymptomatic, 57 cases were imported cases (90.48%), 36 cases were reported by cluster epidemic (57.14%) among friends and relatives. Cases have been spread to the fourth generation. Conclusion: The time sequence transmission map and the cases travel track showed that, in the research area, the epidemic situation of COVID-19 was mainly caused by imported case, and the clustering transmission was the major spread model. The time sequence transmission map and the cases travel track are worth popularizing in the prevention and control of major infectious diseases.

Matrilin-3 alleviates extracellular matrix degradation of nucleus pulposus cells via induction of IL-1 receptor antagonist.

OBJECTIVE: The intervertebral disc contains abundant extracellular matrix (ECM) imbued with proteoglycans, collagens, and water. With the development of intervertebral disc degeneration (IVDD), the ECM undergoes changes characterized by loss of water content, proteoglycans, and collagen content. The purpose of this study was to explore the vital role of Matrilin-3, an ECM protein involved in the progress of IVDD. MATERIALS AND METHODS: NP cells were isolated from the patients' disc samples and exposed to recombinant human (rh)-Matrilin-3 protein (MATN3), and IL-1ß is used as a reducer of nucleus pulposus (NP) cells degeneration. Matrilin-3 and IL-1 receptor antagonist (IL-1Ra) were knocked down by siRNA transfection. Messenger RNA expressions of IL-1Ra, Collagen II, aggrecan, MMP-13, and ADAMTS-5 were determined using Real-Time quantitative Polymerase Chain Reaction (RT-qPCR). Later, the protein levels of IL-Ra, Collagen II, and aggrecan were also detected by Western blot. The IL-1Ra, MMP-13, and ADAMTS-5 dose of the supernatants in the culture medium was determined by enzyme linked immunosorbent assay (ELISA). Finally, immunofluorescence was used to expose the expression of Collagen II, aggrecan, and Collagen X. RESULTS: It was found that the expression of IL-1Ra was markedly increased in the present of MATN3 or IL-1ß, especially these two at once. Besides, MATN3 could upregulate Collagen II and aggrecan expressions, as well as inhibit the MMP-13 and Collagen X production of NP cells. However, the protective effects of Collagen II and aggrecan were abolished after Matrilin-3 silenced. Furthermore, IL-1ß downregulated the Collagen II and aggrecan but promoted the MMP-13 and Collagen X levels of NP cells, which were antagonized by the action of MATN3. Surprisingly, silencing of IL-1Ra significantly abolished the MATN3-induced the protective effects of ECM in NP cells. CONCLUSIONS: This study provides a novel viewpoint of Matrilin-3 in the ECM stability of NP due to its ability to activate IL-1Ra. It is considered that MATN3 efficiently protects ECM degeneration of human NP cells related to maintain the content of Collagen II and aggrecan, as well as inflammatory inhibition.

Spatial-temporal assessment of agricultural virtual water and uncertainty analysis: The case of Kazakhstan (2000-2016).

In this study, a fuzzy-vertex-based virtual-water analysis method (FVAM) is developed for assessing the virtual water content (VWC) of main agricultural products, imports, and exports at a national scale. FVAM has advantages in quantifying state-level VWC with a bottom-up approach and reflecting uncertain parameters based on vertex analysis technique. FVAM is applied to a real case of Kazakhstan in Central Asia. Results reveal that (i) the VWC of Kazakhstan's agricultural products is between 55.61 and 83.98 billion m3/yr in 2000-2016, where wheat is the largest water consumer and the Kostanay state has the largest VWC; (ii) Kazakhstan is a net exporter of virtual water, most of which flows to neighboring countries such as Russia and Azerbaijan; (iii) uncertainties in crop coefficient (Kc), feed water requirement (FWR), drinking water requirement (DWR) and service water requirement (SWR) can affect the VWC assessment; (iv) the massive export of water-intensive products makes the water resources more severe in Kazakhstan, which further squeezes the local ecological water use. Therefore, reducing the export of virtual water should be the focus of future agricultural policies. The findings are useful for decision makers to optimize Kazakhstan's agricultural structure, mitigate the national water scarcity, and facilitate the regional sustainable development.

Branched-chain volatile fatty acids and folic acid accelerated the growth of Holstein dairy calves by stimulating nutrient digestion and rumen metabolism.

The combined addition of branched-chain volatile fatty acids (BCVFAs) and folic acid (FA) could improve growth performance and nutrient utilization by stimulating ruminal microbial growth and enzyme activity. This study was conducted to evaluate the effects of BCVFA and FA addition on growth performance, ruminal fermentation, nutrient digestibility, microbial enzyme activity, microflora and excretion of urinary purine derivatives (PDs) in calves. Thirty-six Chinese Holstein weaned calves (60 ± 5.4 days of age and 107 ± 4.7 kg of BW) were assigned to one of four groups in a randomized block design. Treatments were control (without additives), FA (with 10 mg FA/kg dietary DM), BCVFA (with 5 g BCVFA/kg dietary DM) and the combined addition of FA and BCVFA (10 mg/kg DM of FA and 5 g/kg DM of BCVFA). Supplements were hand-mixed into the top one-third of total mixed ration. Dietary concentrate to maize silage ratio was 50 : 50 on a DM basis. Dietary BCVFA or FA addition did not affect dry matter intake but increased average daily gain (ADG) and feed conversion efficiency. Ruminal pH and ammonia N were lower, and total volatile fatty acids (VFAs) concentration was higher for BCVFA or FA addition than for control. Dietary BCVFA or FA addition did not affect acetate proportion but decreased propionate proportion and increased acetate to propionate ratio. Total tract digestibility of DM, organic matter, CP and NDF was higher for BCVFA or FA addition than for control. Dietary BCVFA or FA addition increased activity of carboxymethyl cellulase and cellobiase, population of total bacteria, fungi, Ruminococcus albus, R. flavefaciens, Fibrobacter succinogenes and Prevotella ruminicola as well as total PD excretion. Ruminal xylanase, pectinase and protease activity and Butyrivibrio fibrisolvens population were increased by BCVFA addition, whereas population of protozoa and methanogens was increased by FA addition. The BCVFA × FA interaction was significant for acetate to propionate ratio, cellobiase activity and total PD excretion, and these variables increased more with FA addition in diet without BCVFA than in diet with BCVFA. The data indicated that supplementation with BCVFA or FA increased ADG, nutrient digestibility, ruminal total VFA concentration and microbial protein synthesis by stimulating ruminal microbial growth and enzyme activity in calves.

[Characteristic and prognostic significance of leukemia stem cells associated antigens expressions in t (8;21) acute myeloid leukemia].

Objective: To investigate the characteristic and prognostic significance of leukemia stem cells associated antigens expressions including CD34, CD38, CD123, CD96 and TIM-3 in t (8;21) AML. Methods: Bone marrow samples of 47 t (8;21) AML patients were collected at diagnosis from October 2015 to April 2018 in Peking University Peoples' Hospital, then flow cytometry method was performed to detect the expression frequencies of CD34, CD38, CD123, CD96 and TIM-3 to analyze the relationship between leukemia stem cells associated antigens expressions and relapse. Results: Of 47 t (8;21) AML patients tested, the median percentages of CD34(+)CD38(-), CD34(+) CD38(-)CD123(+), CD34(+)CD38(-) CD96(+) and CD34(+) CD38(-) TIM-3(+) cells among nucleated cells were 2.37%, 0.24%, 0.27% and 0.06%, respectively. All the frequencies of CD34(+)CD38(-), CD34(+)CD38(-)CD123(+), CD34(+)CD38(-)CD96(+) and CD34(+) CD38(-)TIM-3(+) cells had no impact on the achievement of CR after the first course of induction. All higher frequencies of CD34(+)CD38(-), CD34(+)CD38(-)CD123(+), CD34(+)CD38(-)CD96(+) cells were related to higher 2-year CIR rate. Whereas, the frequency of CD34(+) CD38(-) TIM-3(+) cells had no impact on CIR rate. Both high frequency of CD34(+) CD38(-) cells and the high level of minimal residual diseases (patients with <3-log reduction in the RUNX1-RUNX1T1 transcript level after the second consolidation therapy) were independent poor prognostic factors of CIR[P=0.025, HR=6.9 (95%CI 1.3-37.4) ; P=0.031, HR=11.1 (95%CI 1.2-99.2) ]. Conclusion: Different leukemia stem cells associated antigens had distinct prognostic significance in t (8;21) AML. High frequencies of CD34(+) CD38(-), CD34(+) CD38(-) CD123(+) and CD34(+)CD38(-)CD96(+) cells at diagnosis predicted relapse in patients with t (8;21) AML.

Enhanced expression of circular RNA hsa_circ_000984 promotes cells proliferation and metastasis in non-small cell lung cancer by modulating Wnt/ß-catenin pathway.

OBJECTIVE: In recent years, several circular RNAs (circRNAs) have been identified to play important roles in human cancers. However, the exact effects and molecular mechanisms of circRNAs in non-small cell lung cancer (NSCLC) progression are still unknown. In this study, we aimed to investigate the effect of circular hsa_circ_000984 on NSCLC. PATIENTS AND METHODS: Quantitative real-time PCR was performed to detect the expression levels of hsa_circ_000984 in NSCLC tissues and cell lines. The associations between the expression of hsa_circ_000984 and clinicopathological parameters and patients' survival were analyzed. The cell growth was detected by CCK-8 assay and colony formation assay. Cell migration and invasion assays were used to study the changes in cell migration and invasion capacity. Western blot was performed to analyze the possible relationship between hsa_circ_000984 and the genes downstream of the Wnt/ß-catenin pathway. RESULTS: We found that hsa_circ_000984 was highly expressed in NSCLC tissues and cell lines and correlated with advanced TNM stage and lymph nodes metastasis. The clinical assays indicated that patients with high hsa_circ_000984 expression had shorter overall survival and disease-free survival. The functional investigations showed that the knockdown of hsa_circ_000984 suppressed NSCLC cells proliferation, migration, invasion, and EMT. Moreover, hsa_circ_000984 displayed its oncogenic roles by modulating the activation of Wnt/ß-catenin pathway, which was demonstrated by measuring the expression levels of, ß-catenin, c-myc, and cyclin D1. CONCLUSIONS: Our findings may facilitate a better understanding of hsa_circ_000984, and it might be a potential prognostic biomarker and treatment target for NSCLC patients.

[Minimal residual disease in adults with Philadelphia chromosome negative acute lymphoblastic leukemia in high-risk].

Objective: To explore the significance of minimal residual disease (MRD) in predicting prognosis and guiding therapy of adults with Philadelphia-chromosome negative acute lymphoblastic leukemia (Ph(-) ALL) in high-risk. Methods: Data of newly diagnosed adults with Ph(-) ALL in high-risk who achieved CR were reviewed. Variables associated with outcome were identified by COX regression model and Landmark analysis. Results: A total of 177 patients, 99 (56%) cases male with a median age of 40 years (range, 16-65 years) were included in this study. Of them, 95 (54%) patients received allo-HSCT in CR(1). Multivariate analyses showed that MRD negativity after the first cycle of consolidation (HR=0.52, 95%CI 0.30-0.89, P=0.017) and achieving CR within 4 weeks (HR=0.43, 95%CI 0.24-0.79, P=0.006) were the factors significantly-associated with longer DFS, and allo-HSCT was associated with both longer DFS (HR=0.13, 95%CI 0.08-0.22, P<0.001) and OS (HR=0.24, 95%CI 0.15-0.41, P<0.001) . Landmark analysis was performed on 121 patients, of 85 patients achieving MRD negativity after the first cycle of consolidation, multivariate analyses showed that MRD negativity after the third cycle of consolidation was significantly-associated with longer DFS (HR=0.18, 95%CI 0.05-0.64, P=0.008) and OS (HR=0.14, 95%CI 0.04-0.50, P=0.003) . For the patients achieving MRD negativity after both the first and the third cycles of consolidation, the 3-year DFS rate in the allo-HSCT cohort had a higher trend compared with that in the chemotherapy cohort (75.2% vs 51.3%, P=0.082) , however, the 3-year OS rates in the 2 cohorts were similar (72.7% vs 68.7%, P=0.992) . In those with MRD positivity after the first and/or the third cycle of consolidation, 3-year DFS (64.8% vs 33.3%, P=0.006) and OS (77.0% vs 33.3%, P=0.028) rates in the allo-HSCT cohort were significantly higher than those in the chemotherapy cohort, and similar to those in the cohort achieving MRD negativity after both the first and the third cycles of consolidation and receiving allo-HSCT. Conclusions: MRD negativity after the first cycle of consolidation was a predictor for better outcome in adults with Ph(-) ALL in high-risk. The survival advantage of the allo-HSCT cohort was not pronounced compared with that in the chemotherapy cohort even in those with high-risk features but achieving MDR negativity after both the first and third cycles of consolidation. However, allo-HSCT could be a good option for the patients with MRD positivity after the first and/or the third cycle of consolidation.

[Surveillance of human intestinal parasitic diseases in Nanping City from 2014 to 2018].

OBJECTIVE: To investigate the status of human intestinal parasitic diseases in Nanping City from 2014 to 2018, so as to provide reference for the development of the effective control measures. METHODS: Administrative villages were selected using the two-stage cluster sampling in Nanping City from 2014 to 2018, and surveillance of human intestinal parasitic diseases was performed in 5 administrative villages in each county (district) of Nanping City. Intestinal parasitic infections were detected using a modified Kato-Katz thick smear method (two smears for a single stool sample) in villagers, and the hookworm species was differentiated. In addition, the eggs of Enterobius vermicularis were detected using the adhesive tape method in children aged 3 to 6 years. RESULTS: A total of 6 317 villagers were detected in Nanping City from 2014 to 2018, and the overall prevalence of human intestinal parasitic infections was 2.15%. There was year- (χ2 = 10.53, P < 0.05) and gender-specific prevalence of human intestinal parasitic infections in Nanping City during the study period (χ2 = 17.00, P < 0.01). The prevalence of human intestinal parasitic infections increased with age, and there was age-specific prevalence of human intestinal parasitic infections in Nanping City (χ2 = 102.62, P < 0.01). A total of 945 children at ages of 3 to 6 years were detected, and the prevalence of E. vermicularis infection was 3.28%. CONCLUSIONS: The prevalence of human intestinal parasitic infections is at a low level in Nanping City from 2014 to 2018, and the infection mainly occurs in villagers of advanced age and low education levels. Further comprehensive measures are required to control intestinal parasitic infections in key populations.